The key role of hepatology providers in optimizing reproductive care in patients with liver disease: A call to action
Authors: Ani Kardashian, Tatyana Kushner, Jennifer S. Au, Jennifer A. Flemming, Janet Gripshover, Andrew J. Muir, Susan L. Orloff, Erica Villa, Monika Sarkar
Journal: Hepatology (2023)

The number of pregnancies in women with chronic liver disease (CLD), including in women with cirrhosis and transplant, is rising.1,2 Pregnancies in many of our patients can be safe, although preconception planning is critical to ensure favorable outcomes for mothers and infants. Furthermore, sexually active adolescents and women who do not desire pregnancy should be aware of, and have access to, the breadth of contraceptive options that are most effective and safe in the context of the patient's specific liver condition. This is particularly important given changes to abortion access in the US which may limit the ability to terminate unintended pregnancies.3 The recently published AASLD Reproductive Health in Liver Disease Guidance provides a comprehensive discussion of preconception management for patients with liver disease who are planning pregnancy, or are currently pregnant.4 The aim of the current White paper is to address, in more depth, key management points at the crossroads of reproductive health and liver disease in order to help optimize pregnancy outcomes for mothers and infants, while reducing rates of unplanned and undesired pregnancies in our medically complex patient population (Figure 1).FIGURE 1: Patient-provider relationship and roles in reproductive counseling.ROUTINE INQUIRY OF SEXUAL ACTIVITY AND PREGNANCY INTENTIONS Why reproductive counseling matters In the setting of liver disease, patients may have irregular menstrual cycles or no longer have menstrual cycles, and the potential to get pregnant may not come to mind for these patients or to their health care providers. Moreover, patients with CLD or prior liver transplant have unique risks with pregnancy, including the potential for worsening of underlying liver disease, increased obstetric and/or perinatal complications, and/or use of liver-related medications that are not safe in the setting of pregnancy or breastfeeding.4 For example, in women with cirrhosis, the physiologic changes of pregnancy can exacerbate portal hypertension. Planning of these pregnancies can facilitate preconception variceal screening and treatment, thereby lowering the risk of life-threatening variceal hemorrhage during pregnancy. For some conditions, such as autoimmune hepatitis or after liver transplant, stability of liver disease is necessary for reducing liver dysfunction during pregnancy, and women are advised to delay pregnancy for at least a year after achieving stable liver function. For transplant recipients, pregnancies can occur within weeks of their operation, and early inquiry about sexual activity and contraceptive discussion can lower the risks of unplanned pregnancies during this early and high-risk postoperative period. In that vein, pregnancy planning allows hepatology providers to identify medications that are dangerous to the growing fetus, such as mycophenolic acid products, which are highly teratogenic and increase the risks of miscarriage. In addition, planning of pregnancies in women with liver disease allows time to transition to regimens that are safe for pregnancy and breastfeeding, while ensuring the stability of liver disease on new treatment regimens before conception. Finally, preconception counseling by hepatology providers also ensures that patients are informed of pregnancy-related risks in the context of their specific liver condition, including referral to high-risk obstetricians for multidisciplinary discussions. These steps ultimately empower patients to make educated decisions regarding whether they wish to pursue pregnancy and the recommended testing and medication adjustments to optimize pregnancy outcomes. Improving our practice For medically complex patients, the addition of reproductive counseling may seem beyond the scope of what can be covered in a single clinic visit. However, there are some simple measures that can help to enhance routine inquiry and documentation of family planning intentions, and ensure patients are referred to the appropriate providers for more nuanced discussions. A recent liver transplant study evaluated patient preferences regarding the receipt of reproductive health counseling and identified discussions with transplant providers as the single most favored modality by patients for learning about pregnancy and contraception options.5 This finding underscores the sentinel role of hepatology providers in the global decision-making of our patients, which extends beyond liver-specific inquiries. In this study, providers were also asked about modalities that could help to improve their routine inquiry of sexual activity, family planning, and contraception. High yield options included the addition of "family planning" on the problem list or within clinic note templates, with automatic prompts reminding providers to inquire and document contraception use and pregnancy planning. Educational materials were also deemed helpful by patients and providers, thus having pamphlets in a clinic or online links to share with patients is another efficient option that can complement provider discussions. The patient-friendly version of the AASLD Reproductive Health and Liver Disease Guidance is one such resource that covers family planning considerations in patients with liver disease, including contraceptive options and pregnancy planning, with digestible language and figures for patient-level explanations.5 Providers may choose to share with their patients the section of the Guidance document that is pertinent to their patient's liver condition. INCREASING CONTRACEPTION KNOWLEDGE AND ACCESS For adolescents and women whose personal preference is to avoid pregnancy, or who have undue health-related risks of pregnancy, there is a critical need to ensure access to the breadth of contraceptive options that are safe for their specific liver condition. This is particularly important for adolescent patients and those in our underserved communities for whom unplanned pregnancies that are also undesired by patients may have greater psychosocial consequences and pose additional barriers to caring for one's own chronic liver disease.6,7 Patient-centered decision-making for contraceptive selection also increases adherence and patient satisfaction with selected agents, which further helps to lower contraceptive failure rates. Although the nuances of contraceptive management are beyond the scope of practice for most hepatology providers, a few basic principles regarding contraceptive safety, efficacy, and access in liver disease can help to increase contraceptive uptake among patients who are interested in these options. Dispelling contraceptive myths and working with prescribers As detailed in the AASLD Reproductive Guidance, all forms of progestin-only contraception, including the hormonal intrauterine devices (IUDs) are considered safe regardless of liver disease etiology or severity. However, there remain pervasive misconceptions about their safety. In the setting of transplant, for example, we identified misconceptions among transplant providers regarding the perceived dangers of IUDs in liver transplant recipients, which likely stems from older case reports noting unintended pregnancies with initial devices.8 Historical concerns also include the risk of pelvic inflammatory disease with foreign body insertion in immunocompromised patients, although we now know that IUDs confer no greater pelvic inflammatory disease risk in immunocompromised women than in IUD nonusers. In additiona, copper IUDs were historically avoided in women with Wilson disease, however, the systemic absorption of copper is minimal and therefore need not influence the choice of contraception. Estrogen-containing agents do have some distinct risks that preclude safe use in adolescents and women with certain liver diseases, namely decompensated cirrhosis, Budd Chiari syndrome, hepatocellular adenomas, and liver transplant recipients with graft failure. However, the majority of our patient population can safely use these agents, which come in formulations such as a pill, skin patch, or vaginal ring. Older preparations of estrogen-containing agents had much higher estrogen doses, which did increase the risk of elevated liver tests, thus underlying liver disease was once a contraindication to their use. However, contemporary preparations have no greater risk of elevated liver tests compared with placebo.9 In the recent liver transplant survey, misconceptions about estrogen safety persisted, including the belief that these should be avoided in transplant recipients.8 Thus, there is a need to dispel contraception myths within our field, and to work closely with prescribing colleagues in primary care, pediatrics, and women's health, to optimize timely initiation and access to the spectrum of safe contraceptive options that are acceptable to our patients. Increasing access to emergency contraception (EC) EC reflects agents that reduce the chance of pregnancy when used within the first 5 days after sexual intercourse. It is important that hepatology providers be aware of local policies regarding abortion access, as EC must be used in a timely manner following unprotected intercourse if a patient does not desire pregnancy and does not have access to pregnancy termination. EC options include the copper or higher dose hormonal IUD, the progestin-only levonorgestrel pill, or ulipristal acetate, a progesterone receptor modulator. All of these agents can be used in patients with liver disease, regardless of the etiology or severity of their liver condition. Furthermore, levonorgestrel pills do not require a prescription and can be obtained over the counter at most pharmacies. In the case of EC failure or unintended pregnancy, patients may consider medical (ie, use of misoprostol or mifepristone by oral or vaginal administration) or surgical (ie, dilation and curettage) termination depending on the availability of these options in their state of residence. Both options are considered safe for women with CLD. Informing patients of these options before unprotected intercourse can also empower patients in their reproductive decision-making. In conclusion, as the number of pregnancies in women with CLD rises, it is becoming increasingly important for hepatology providers to offer reproductive counseling to their patients to improve maternal and fetal outcomes. In some areas of the US, pregnancy termination may be limited, thus it is important to routinely inquire about sexual activity and pregnancy intentions in adolescents and reproductive-aged women and ensure our patients have up-to-date knowledge about safety and access to routine and EC. Only by prioritizing reproductive health in our most complex patients with CLD will we uphold the sanctity of the patient-provider relationship, honor our patients' wishes, and optimize health outcomes for mothers and infants.